Non-ionic Gd-based MRI contrast agents are optimal for encapsulation into phosphatidyldiglycerol-based...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Radiology

Background:

• Thermosensitive liposomes (TSL) encapsulate contrast agents (CAs) for MRI-guided thermotherapy.
• Six clinically approved gadolinium-based CAs were evaluated for TSL formulation.

Purpose of the Study:

• To assess the feasibility of formulating TSL with six different MRI CAs.
• To characterize the T(1) relaxivity, permeability, and stability of these TSL formulations.
• To identify optimal CA characteristics for MRI-assisted thermotherapy.

Main Methods:

• Passive encapsulation of CAs into dipalmitoyl-sn-glycero-3-phosphocholine/distearoyl-sn-glycero-3-phosphocholine/dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG(2)) TSL.
• Determination of T(1) relaxivity (r(1)), diffusive water permeability (P(d)), and shelf-life stability.
• Evaluation of TSL performance across a temperature range relevant to thermotherapy.

Main Results:

• All TSL formulations were stable, monodispersed, and unaffected by CA encapsulation in terms of zeta potential and phase transition temperature.
• TSL exhibited temperature-dependent r(1) increases between 38-44°C, correlating with the lipid phase transition.
• Non-ionic CAs (Gd-BT-DO3A, Gd-DTPA-BMA, Gd-HP-DO3A) showed lower P(d) at physiological temperatures.
• Most CAs induced phospholipid hydrolysis, leading to leakage, except Gd-DTPA-BMA.
• Serum proteins increased P(d) at 30°C.
• High CA concentration is essential for significant r(1) change during heat-triggered release.

Conclusions:

• Non-ionic CAs with low osmolality are preferred for TSL formulation in MRI-assisted thermotherapy.
• Gd-DTPA-BMA demonstrated good stability and permeability characteristics, making it a promising candidate.
• Optimized TSL formulations require careful CA selection to balance relaxivity, stability, and controlled release for effective thermotherapy.